This application claims the benefit of priority from U.S. Provisional Patent Application No. 61/785,445 filed on Mar. 14, 2013 and entitled “Method for Forming Materials In Situ Within a Medical Device,” the full disclosure of which is incorporated herein by reference.
Abdominal Abdominal Aortic Aneurysms (AAA) are weakened areas in the aorta that form balloon-like bulges, or sacs, in approximately the abdominal area. As blood flows through the aorta, the pressure of the blood pushes against the weakened wall, causing it to enlarge and often rupture. Ruptured AAA is a major cause of death in the United States.
In the past, clips and open surgery were the traditional interventional treatments for AAA. More recently, endografts, sometimes with stents for added stability, have been placed across the aneurysm to reduce the pressure on the aneurysm wall and prevent its enlargement and rupture.
Most recently, there have been described systems wherein an expandable member of a device is introduced into the aneurysmal sac by means of minimally invasive surgical (MIS) techniques, e.g., guidance through the vasculature of a human patient using a guidewire introduced into the patient for that purpose. Flowable precursor materials are introduced into the expandable member, the precursor materials undergo chemical reaction and cause the expandable member to expand and conform to the shape of the aneurysmal sac. As the materials harden, they lock the expandable member in place in the patient and stabilize the aneurysm. See for example, U.S. Pat. Nos. 7,872,068; 8,044,137; and U.S. 2006/0222596, the contents of which are hereby incorporated by reference herein in their entirety. The expandable member may be, for example, a single-walled or double-walled balloon or an inflatable cuff. Other examples of devices having an inflatable or expandable member are provided, for example, in PCT Application Pub. No. WO 00/51522, U.S. Pat. Nos. 5,334,024; 5,330,528, 6,1312,462; 6,964,667; 7,001,431; 2004/0204755; and 2006/0025853A1, the contents of which are hereby incorporated by reference herein in their entirety. The flowable precursor materials are typically polymer precursors which polymerize and cross-link to form hydrogels. One preferred type of polymer precursor is a material that can be polymerized by free radical polymerization. Typically this involves the polymerization/cross-linking of two prepolymers, each having terminal reactive groups that are susceptible to free radical polymerization, such as acrylates and methacrylates.
The polymerization is effected by combining both prepolymers with a thermally activated low temperature free radical initiator and an initiator catalyst at physiological temperature.
In order to avoid premature polymerization, i.e., prior to mixing all the components and allowing them to polymerize in situ in the expandable device, the components are typically stored in two separate aqueous solutions, one solution comprising one polymer precursor and the free radical initiator, and the other solution comprising the other polymer precursor and the initiator catalyst. In this way, the two polymer precursors are kept apart, as are the free radical initiator and the initiator catalyst.
In practice, the two solutions are concomitantly delivered and then mixed, either ex vivo in a manifold, or in the expandable device itself.
Because of the instability of thermally activated low temperature free radical initiators, the solutions containing the components must necessarily be kept frozen, i.e., at zero degrees Celsius or lower, until needed. Even so, the useful shelf life of the device or kit comprising such solutions is only 12 to 18 months.
The necessity that the solutions be kept frozen is a serious practical disadvantage, inasmuch as the solutions cannot easily be thawed and be ready for use as soon as a patient presents with an AAA that needs immediate treatment, particularly since rapid thawing by conventional techniques using large temperature differentials, e.g., hot water or microwave defrosting, cannot be used because of the thermal activation of the initiator.
It would be desirable to have materials and methods for using such materials, such that storage of the aqueous solutions used for treatment could be at or near ambient temperature, allowing for immediate use when required, and having a useful shelf life of at least 2 years.
It would further be desirable to be able to administer only one solution, rather than two, thus avoiding the necessity for mixing in a manifold or other device, and ensuring homogeneity of the material being polymerized.